Nucleic acid secondary structures for therapeutic and biomolecular device applications

Abstract

Nucleic acids can form a variety of non-canonical secondary structures, among which G-quadruplexes and i-motifs are well-studied. These non-canonical structures are widespread in the human genome and are primarily found in the telomeric region and the promoter region of numerous proto-oncogenes. Hence, they represent attractive pharmacological targets for anti-cancer therapeutics. Besides, the unique properties of these structures can also be utilized for nano-biotechnology applications. This review highlights the therapeutic targeting of G-quadruplexes and i-motifs by selective ligands endowed with potent biological activities. These novel molecular probes can selectively target DNA secondary structures over duplex DNA and promote cancer cell death. We also outline the development of advanced functional nanostructureslike ion channels, bionanowires, logic gates, and enzyme-regulated DNA-based devices by conjugating G-quadruplex or i-motif with organic scaffolds. This review also focuses on the supramolecular chemistry of nucleic acid components to generate nucleoside-derived hydrogel networks and synthetic ion channels. These studies would provide new dimensions into anti-cancer therapeutics and nanobiotechnology using DNA secondary structures